Nicorandil inhibits TLR4/MyD88/NF-κB/NLRP3 signaling pathway to reduce pyroptosis in rats with myocardial infarction.

Pyroptosis is an inflammatory cell death that regulates cardiomyocyte loss after myocardial infarction. Reports indicate that nicorandil has a strong anti-inflammatory effect and protects the myocardium from myocardial infarction. However, its relationship with pyroptosis is largely unreported. Here, we investigated to influence and mechanism of action of nicorandil on cardiomyocyte pyroptosis. Forty Sprague Dawley rats were randomly assigned to sham, MI, MI + nicorandil, and MI + nicorandil + TAK242 groups (10 per group). Myocardial infarction modeling was performed through ligation of the anterior descending branch of the left coronary artery. The function of cardiac was evaluated through echocardiography, detection of myocardial adenine nucleotides, cTnI, LDH, TTC, and HE staining. Moreover, we used qRT-PCR, immunohistochemistry, and Western blotting to examine the expression of pyroptosis-related molecules and the inflammasome pathway of TLR4/MyD88/NF-κB/NLRP3. Myocardial infarction caused the activation of GSDMD, aggravated myocardial injury, and triggered cardiac dysfunction. Myocardial infarction induced pyroptotic cell death, manifested as upregulation in mRNA and protein levels associated with pyroptosis, including caspase-1 cleavage and increased expression of IL-1ß and IL-18. These changes were mitigated by nicorandil. The achieved data implicate that myocardial infarction induces pyroptosis via the TLR4/MyD88/NF-κB/NLRP3 pathway, which can be inhibited by nicorandil pretreatment. Therefore, nicorandil exerts cardioprotective effects by activating KATP channels, and at least in part through inhibition of the TLR4/MyD88/NF-κB/NLRP3 pathway to reduce myocardial infarction-induced pyroptosis. As such, it is a potential therapy for ischemic heart disease.

Puerarin pretreatment inhibits myocardial apoptosis and improves cardiac function in rats after acute myocardial infarction through the PI3K/Akt signaling pathway.

BACKGROUND: Puerarin demonstrates a protective effect in many cardiovascular diseases. However, the role of puerarin in acute myocardial infarction (AMI)-induced injury and the exact molecular mechanisms are not fully understood. OBJECTIVES: To investigate whether puerarin pretreatment improves cardiac function and to study the mechanism of action of puerarin. MATERIAL AND METHODS: Thirty rats were grouped into sham group, AMI group and AMI+puerarin (PUE) group at random (n = 10 per group). Except for the sham group, a model of AMI was established via left anterior descending artery ligation. The PUE group received puerarin 120 mg/(kg × day) for 7 days before the operation. Echocardiography was used for evaluation of cardiac function in rats and TUNEL staining for measuring myocardial apoptosis. The expression levels of p-PI3K, t-Akt, p-Akt, Bax, Bcl-2, and cleaved caspase-3 proteins were measured with western blot. RESULTS: Compared to the sham group, the AMI group demonstrated poor cardiac function and decreased p-PI3K, p-Akt and Bcl-2 proteins levels, while Bax, cleaved caspase-3, and myocardial apoptosis levels increased. Compared with the AMI group, the PUE group showed significant improvement in cardiac function and increased protein expression of p-PI3K, p-Akt and Bcl-2, while Bax and cleaved caspase-3 levels decreased and myocardial apoptosis was attenuated. CONCLUSIONS: Puerarin pretreatment in AMI can effectively improve cardiac function by inhibiting myocardial apoptosis. The molecular mechanism of this protective effect may be mediated by activating the PI3K/Akt pathway in cardiomyocytes.

Prognostic value of plasma brain natriuretic peptide value for patientswith sepsis: A meta-analysis.

PURPOSE: The aim of this meta-analysis was to clarify the diagnostic role of plasma BNP and NT-proBNP in predicting mortality for septic patients. METHODS: A systematic review was conducted prior to January 2018. Summary sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) of the prognostic value of plasma BNP and NT-proBNP for septic patients. The area under the receiver operating curves (AUROC) were used to summarize overall test performance. RESULTS: Twenty-two studies with 3417 septic patients were selected in the analysis. The summary sensitivity, specificity, PLR, NLR, DOR and the AUROC of the overall analysis of BNP were: 0.84, 0.73, 3.1, 0.22, 14, 0.85; and these values of NT-proBNP were: 0.71, 0.73, 2.6, 0.39, 7 and 0.7 respectively; Subgroup analysis and meta-regression analyses showed that the tested method and observation endpoint influenced the summary sensitivity, specificity of BNP, but the tested day, tested method or observation endpoint did not influence the summary sensitivity, specificity of NT-proBNP. CONCLUSIONS: This meta-analysis indicates that both elevated plasma BNP and NT-proBNP have moderate predicts value for the mortality of septic patients, and the tested method and observation endpoint influence the results of BNP.

Clinical features, risk factors, and treatment experience: a review of 74 patients with ST-segment elevation myocardial infarction complicated by ventricular fibrillation.

BACKGROUND: Ventricular fibrillation (VF) is one of the most serious complications of acute myocardial infarction, with a high mortality rate. There is a lack of value of rescue thrombolysis in ST-segment elevation myocardial infarction (STEMI) complicated by VF. OBJECTIVE: To examine the relationship between risk factors and mortality, and assess the value of rescue thrombolysis in STEMI complicated by VF. METHODS: A total 74 cases of STEMI complicated by VF were enrolled. The experimental group consisted of 26 patients who underwent rescue thrombolysis, and the control group included 48 cases without rescue thrombolysis. The two groups were compared in terms of demographic and clinical features including gender, age, onset time, blood pressure, patient's history, creatine kinase-MB, infarct area, complications, therapy, and outcomes, including mortality. RESULTS: The mortality rate of the experimental group was 15.38%, lower than 37.50% of the control group (p < 0.05). The bleeding rate was 34.62% (n = 9) in the experimental group. The risk factors of smoking, shock, and rescue thrombolysis were correlated with mortality of STEMI complicated by VF (p < 0.05 for all): Smoking and shock both were positively correlated with mortality, their regression coefficients/odds ratios (OR) were, respectively, 4606/100,041 and 5552/247,711; the rescue thrombolysis was negatively correlated with mortality, its regression coefficient/OR was -1942/0.143. CONCLUSIONS: Rescue thrombolysis combined with cardiopulmonary resuscitation and defibrillation is beneficial to patients with STEMI complicated by VF. Smoking, shock upon admission, and lack of rescue thrombolysis were risk factors for mortality in STEMI complicated by VF.

Clinical features and treatment experience: a review of 292 Chinese cobra snakebites.

Although Chinese cobra snakebite is the most common type of snake venenation in China, it still lacks a comprehensive and systematic description. Hence, we aimed to study Chinese cobra bite cases with particular attention to demography, epidemiology and clinical profile. In this study, a total of 292 cases of Chinese cobra snakebite, presenting between January 1, 2008 and December 31, 2012, were retrospectively reviewed. To investigate the effect of treatment at different presentation times (time from snakebite to admission), the patients were divided into two groups: group A included 133 cases that presented <12 h after the bite; group B included 159 cases that presented ≥12 h after the bite. To assess the correlation between application of a tourniquet and skin grafting, the cases were re-divided into two groups according to whether or not a tourniquet was used after the snakebite: tourniquet group (n=220) and non-tourniquet group (n=72). The results showed that Chinese cobra snakebites were most commonly seen during the summer, in the upper limbs, and in males, young adults, and snake-hunters. Group A experienced milder intoxication than group B (P<0.001). The rate of skin grafting was significantly higher in the tourniquet group (20.0%, compared with 9.7% in the non-tourniquet group, P<0.05). The results of this study indicate that anti-cobra venom and swift admission (within 12 h of the snakebite) are recommended for Chinese cobra snakebite. Tourniquet use is not recommended.

[Cox regression analysis on influencing factors of coronary heart disease among people over 40 years of age].

OBJECTIVE: To explore the affecting factors on coronary heart disease among people over 40 years of age in Guangxi area, China. METHODS: Baseline data was gathered through the Third National Blood Pressure Survey in 1991 in China. A total number of 11 818 adults over 40 years old had been studied in Guangxi province. Data of morbidity and mortality of coronary heart disease was obtained. RESULTS: Cardiovascular events were related to systolic blood pressure, diastolic blood pressure, pulse pressure, smoking, BMI regardless of their myocardial infarct (MI) history. Cox regression analysis showed that the relative risk for cardiovascular events increased by 21 [95% confidence interval (CI): 9.06-48.44] times for those people having MI history. When pulse pressure, systolic blood pressure, diastolic blood pressure increased by every 10 mm Hg, the relative risk for cardiovascular events increased by 1.29 (95% CI: 1.11-1.49), 1.18 (95% CI: 1.02-1.22), 1.13 (95% CI: 1.05-1.28) respectively. There was 1.23 (95% Cl: 1.05-1.45) times higher in smoker than non-smoker on relative risk for cardiovascular events. When BMI increasing 1, the relative risk for cardiovascular events would increase 1.03 (95% CI: 1.01-1 .05) times. CONCLUSION: Hypertension, smoking, increase of BMI were the risk factors of coronary heart disease among people who were over 40 years of age.